Possible Cognitive Dysfunction Associated With High-Dose Fluoxetine in a Patient on Lithium

Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, are widely prescribed medications. Fluoxetine is considered a first-line pharmacological treatment for common psychiatric conditions such as anxiety, depression, and obsessive-compulsive disorder (OCD). In large clinical trials, fluoxetine has consistently demonstrated a strong safety and tolerability profile over the past 30 years. This case describes a 36-year-old Caucasian female with a history of autism spectrum disorder (ASD) and bipolar I disorder treated with lithium, who developed new-onset cognitive dysfunction following the up-titration of fluoxetine. Her fluoxetine dose was gradually titrated to 80 mg/day over several weeks, in accordance with dosing guidelines. At that dose, she began experiencing progressive memory loss and confusion, ultimately requiring hospitalization. Extensive evaluation ruled out other potential psychiatric or medical causes of cognitive decline. Upon discontinuation of fluoxetine and reduction of her longstanding lithium dose, her cognitive function improved after 2 weeks and returned to baseline within 4 weeks. While SSRIs are generally well-tolerated compared to other antidepressant classes, isolated reports suggest fluoxetine may be associated with reversible memory impairment in certain populations. This is the first documented case of reversible memory loss requiring hospitalization associated with fluoxetine in a middle-aged adult with complex comorbid psychiatric conditions-a demographic frequently prescribed this medication. When prescribing fluoxetine to patients with comorbid psychiatric conditions on lithium, clinicians may consider slow titration and proactive cognitive monitoring.